ABSTRACT This K23 Mentored Patient-Oriented Research Career Development Award proposal supports a 5-year research and training program for Dr. Jenell Stewart to establish herself as an independent investigator with expertise in sexually transmitted infection (STI) and HIV prevention. Dr. Stewart is an Infectious Diseases physician-scientist with a strong track record of dedication to STI and HIV research in low-resource settings and extensive experience in international collaborations. For this proposal, Dr. Stewart will benefit from additional training, including formal course work and mentorship, in design and analysis of STI and HIV prevention trials, assessment of sexual exposures and event-driven adherence, and mixed-methods analysis of gendered power dynamics in adherence behavior. In the past decade, rates of bacterial STIs have increased markedly in populations worldwide. In addition to increased risk of HIV infections, young Kenyan women have very high STI rates with severe consequences (e.g., pelvic inflammatory disease, tubal infertility, complications of pregnancy). Post-exposure prophylaxis (PEP) with the antibiotic doxycycline (dPEP) has been proposed as a novel STI control strategy, and dPEP trials among men who have sex with men are ongoing with one completed and multiple planned. This K23 proposal will leverage the first trial of dPEP among women, launching in Kenya in January 2020. In contrast to other STI prevention strategies that rely on partner participation, on-demand dPEP would be woman-controlled; however, little is known about adherence behavior to STI prevention among Kenyan women. Understanding adherence to HIV pre-exposure prophylaxis (PrEP) in African women was key to accurately defining effectiveness in this population, and similarly dPEP adherence will be important to measure and evaluate. We hypothesize that provision of dPEP with high adherence will substantially reduce the incidence of bacterial STIs, particularly Chlamydia trachomatis as well as Treponema pallidum and Mycoplasma genitalium. The longitudinal evaluation of M. genitalium in women in the parent randomized trial of dPEP will provide unique data on this emerging STI. Aim 1 will measure the effect of dPEP adherence on bacterial STI protection by leveraging a randomized trial of dPEP versus standard risk-reduction counseling among Kenyan women (N=446) followed for 12 months using hair drug concentrations to determine adherence in a comprehensive case-cohort analysis. Aim 2 will assess the impact of a recent diagnosis with an STI from point- of-care STI testing on subsequent longitudinal prevention behavior (adherence to dPEP and PrEP and frequency of condomless sex) using self-reported behavior validated against biological measures. Aim 3 will determine how gendered power dynamics relate to adherence behavior using a mixed methods analysis of quantitative and qualitative measures of gendered power differentials in primary sexual relationships. This proposal will provide important evidence to avert morbidity and mortality from bacterial STI and HIV acquisition among women.